Purpose of review:
Aging is a primary risk factor for the development of osteoarthritis and the understanding of how aging processes contribute to the development of osteoarthritis is an important area of active research. The most recent literature in this area was reviewed in order to update investigators on the status of the field.
The field is beginning to move beyond a cartilage focus to include other joint tissues relevant to osteoarthritis such as ligaments, meniscus, and bone. Synovitis also appears to play a role in osteoarthritis but has not been a focus of aging studies. Studies in small animals, including mice and rats, demonstrate age-related changes that can contribute to osteoarthritis and show that animal age is a key factor to be considered in interpreting the results of studies using surgically induced models of osteoarthritis. There is accumulating evidence that cellular processes such as damage-induced cell senescence contribute to osteoarthritis and a growing body of literature on the role of epigenetic regulation of gene expression in aging and osteoarthritis.
Not all osteoarthritis is due to aging processes in joint tissues, but the age-related changes being discovered certainly could play a major contributing role.
"Inflammatory mediators such as COX2 and NO further contribute to eliciting imbalance between chondrocyte catabolism and anabolism (Houard et al., 2013). Various etiological factors for OA have been noted, including those unrelated to genetics, such as age, obesity, dietary factors , sedentary life style, and injury (Buckwalter and Brown, 2004; Loeser, 2013; Wluka et al., 2013). However, the precise molecular and cellular mechanisms by which these environmental OA risk factors mediate the disruption of cartilage homeostasis remain elusive. "
[Show abstract][Hide abstract] ABSTRACT: Osteoarthritis (OA) is one of the most prevalent forms of joint disorder, associated with a tremendous socioeconomic burden worldwide. Various non-genetic and lifestyle-related factors such as aging and obesity have been recognized as major risk factors for OA, underscoring the potential role for epigenetic regulation in the pathogenesis of the disease. OA-associated epigenetic aberrations have been noted at the level of DNA methylation and histone modification in chondrocytes. These epigenetic regulations are implicated in driving an imbalance between the expression of catabolic and anabolic factors, leading eventually to osteoarthritic cartilage destruction. Cellular senescence and metabolic abnormalities driven by OAassociated risk factors appear to accompany epigenetic drifts in chondrocytes. Notably, molecular events associated with metabolic disorders influence epigenetic regulation in chondrocytes, supporting the notion that OA is a metabolic disease. Here, we review accumulating evidence supporting a role for epigenetics in the regulation of cartilage homeostasis and OA pathogenesis.
"In total, 1.5 million knee arthroscopies are performed annually, and meniscal injuries account for more than 50 % of those operations [21, 22]. The prevalence of meniscal tears increases with age [23••] and may be as high as 56 % in men aged 70–90 years old . Allografts or bio-engineered meniscal substitutes  can be applied after the removal of the meniscus; however, radiological and MRI scans show no protective effect against the development of OA . "
[Show abstract][Hide abstract] ABSTRACT: The most common diseases of the joints and its tissues are osteoarthritis and rheumatoid arthritis, with osteoarthritis being anticipated to be the fourth leading cause of disability by the year 2020. To date, no truly causal therapies are available, and this has promoted tissue engineering attempts mainly involving mesenchymal stem cells. The goal of all tissue repairs would be to restore a fully functional tissue, here a hyaline articular cartilage. The hyaline cartilage is the most affected in osteoarthritis, where altered cell-matrix interactions gradually destroy tissue integrity. In rheumatoid arthritis, the inflammatory aspect is more important, and the cartilage tissue is destroyed by the invasion of tumor-like pannus tissue arising from the inflamed synovia. Furthermore, the fibrocartilage of the meniscus is clearly involved in the initiation of osteoarthritis, especially after trauma. Recent investigations have highlighted the role of migratory progenitor cells found in diseased tissues in situ. In osteoarthritis and rheumatoid arthritis, these chondrogenic progenitor cells are involved in regeneration efforts that are largely unsuccessful in diseased cartilage tissue. However, these progenitor cells are interesting targets for a cell-based regenerative therapy for joint diseases.
Current Rheumatology Reports 11/2014; 16(11):461. DOI:10.1007/s11926-014-0461-4 · 2.87 Impact Factor
"In fact, meniscal injuries are the most common knee injury and account for more than 50% of the 1.5 million knee arthroscopies performed annually (Englund et al., 2008; Lohmander et al., 2007). The prevalence of meniscal tears increases with age (Loeser, 2013) and may be as high as 56% in men aged 70–90 years old (Englund et al., 2008). Lack of robust meniscal repair in adults with or without surgical intervention has led to the development of allografts or bioengineered meniscal substitutes (Haddad et al., 2013; Steinert et al., 2007), and, whereas these fill the space void created following removal of the meniscus, clinical, radiological, and MRI evaluations show no protection against the development of OA (Hommen et al., 2007). "
[Show abstract][Hide abstract] ABSTRACT: Highlights
•Progenitor cells are found in the inner avascular part of human osteoarthritic menisci
•These meniscus progenitor cells (MPCs) are clonogenic, migratory, and multipotent
•MPCs are governed via the canonical TGF-β pathway
•TGF-β3 via Smad2 reduces Runx2 to enhance the chondrogenic potential of MPCs
Degeneration of the knee joint during osteoarthritis often begins with meniscal lesions. Meniscectomy, previously performed extensively after meniscal injury, is now obsolete because of the inevitable osteoarthritis that occurs following this procedure. Clinically, meniscus self-renewal is well documented as long as the outer, vascularized meniscal ring remains intact. In contrast, regeneration of the inner, avascular meniscus does not occur. Here, we show that cartilage tissue harvested from the avascular inner human meniscus during the late stages of osteoarthritis harbors a unique progenitor cell population. These meniscus progenitor cells (MPCs) are clonogenic and multipotent and exhibit migratory activity. We also determined that MPCs are likely to be controlled by canonical transforming growth factor β (TGF-β) signaling that leads to an increase in SOX9 and a decrease in RUNX2, thereby enhancing the chondrogenic potential of MPC. Therefore, our work is relevant for the development of novel cell biological, regenerative therapies for meniscus repair.
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